Post Obstructive Diuresis

Dr. Garima Aggarwal

DM Nephrology ResidentAmrita Institute of Medical Sciences,

Kochi, India

19.09.14

Refers to dramatic increase in urine output after the release of Urinary tract Obstruction.

Factors necessary are

- Accumulation of total body water, Sodium and urea ( or)

- Impairment of Tubular re-absorptive capabilities.

True incidence of Post obstructive diuresis (POD) is not known

Clinically significant POD occurs only in the setting of prior bilateral ureteral obstruction (BUO) or unilateral obstruction of a solitary functioning kidney

Appears uncommon following UUO due to compensation by normally functioning contra-lateral kidney.

• Definition

– High urine output exceeding (>200ml/hr) 0.5-1 L per hour after the obstruction is relieved. • Patients with edema, hypertension, weight gain, and

azotemia are most likely to exhibit this condition.

Postobstructive Diuresis

Types Post obstructive Diuresis is of 2 types:

- Physiological Diuresis

- Pathological Diuresis

- Urea Diuresis ( Uosm > 250)

- Sodium Diuresis ( Uosm > 250)

- Water Diuresis ( Uosm < 150)

Types Physiological Diuresis - Self limiting –

As a response to solute and water overload. Stops after return to euvolumeic state.

Pathological Diuresis - Inappropriate diuresis of water beyond euvolemic state, due to insensitivity of collecting tubule to ADH and other defects in urinary concentrating ability of the kidney and tubular reabsorption of solutes

– Self limiting and can be managed easily

• Urea diuresis

– Is the most common.

– It is self-limiting, lasting 24-48 hours.

–Monitor fluid balance and electrolytes.

–Unless otherwise contraindicated, increased fluid intake should suffice.

• Sodium diuresis –Second most common.

– It usually is self-limiting, potential for longer duration (>72 h).

–Monitor fluid balance and electrolytes more aggressively

• Water diuresis –Rare and self-limiting.

– It is a temporary nephrogenic diabetes insipidus, which occurs secondary to impaired renal tubular response to ADH.

Pathophysiology of

Post Obstructive Diuresis

After the release of obstruction

• Contributing factors are both physiological and pathological

Physiological

1.Excess Na and water retention

2.Retention of urea and non reabsorbable solutes

3.Accumulation of ANP

Pathological

1.Decreased tubular reabsorption of Na

2.Concentration defect

3.Increased tubular flow reducing equilibration time for

reabsorption of Na and water

Derangement of Urinary concentrating ability

• Normal urine concentrating ability requires a hypertonic medullary interstitial gradient because of – active salt reabsorption from the thick ascending limb of Henle, – urea back flux from the inner medullary collecting duct, and – water permeability of the collecting duct mediated by vasopressin and

aquaporin water channels.

• Obstructive nephropathy can disrupt some or all of these mechanisms and lead to deficits in urinary concentration

• The onset of concentration defects may develop soon after obstruction.

Insensitivity to ADH

Another aquaporin, AQUAPORIN 1 (AQP1) - renal proximal tubules, the thin descending limb of Henle, and the descending vasa recta in the kidney. It promotes urinary concentration through the countercurrent multiplier by facilitating water transport from the descending limb of Henle into the interstitium

• Li and coworkers (2001) demonstrated that the polyuria following the release of BUO correlates with a decreased expression of the aquaporin water channels AQP1, AQP2, and AQP3 in rats.

• Jensen and coworkers (2006) examined changes in water channels after bilateral ureteral obstruction in rats. As expected, post-obstructive polyuria with reduced urine osmolality was accompanied by decreased expressions of AQP1, AQP2, and AQP3 compared with control rats.

Thus dysregulation of aquaporin water channels in the proximal tubule, thin descending loop, and collecting duct

may contribute to the long-term polyuria and impaired concentrating capacity caused by obstructive nephropathy.

Defects in Sodium Transport• BUO- sodium and water excretions may be quite robust after

release of obstruction- FENa may be increased to as much as 20 times normal in this setting (Zeidel and Pirtskhalaishvili, 2004)

• In spite of differential quantitative responses between UUO and BUO after release of the obstruction, the reabsorption defects in segmental nephron Na+ transport are similar.

• Active transport of Na+ across cell membranes requires apical entry through selective Na+ transporters or channels and basolateral exit driven by sodium-potassium adenosine triphosphatase (Na+,K+-ATPase) and adequate adenosine triphosphate (ATP) must be generated to drive these primary transport steps.

A marked decrease in amiloride-sensitive oxygen consumption and Na+ entry in isolated cells from the inner medullary collecting ducts of obstructed rabbit kidneys reflects reduced activity of the apical Na channel (ENaC). In addition, ouabain-sensitive transport as measured by oxygen consumption and ATPase activity was shown to be reduced in cells from this portion of the nephron harvested from obstructed kidneys (Hwang et al, 1993a)

• When urine flow is obstructed, upstream Na+ delivery to apical cell membranes slows so that the transmembrane gradient is reduced. This could then serve as the signal for the downregulation of transporter activity or expression resulting in reduced active Na+ transport across the basolateral cell membrane (Zeidel, 1993).

• Ischemia has also been proposed as a signal in this setting, where ischemia that accompanies the reduced perfusion of the kidney with obstruction can also be a mediator of reduced transporter expression. (Kwon et al, 2000)

• *A number of investigators have shown that obstruction markedly increases the endogenous production of PGE2 in the renal medulla- supraphysiologic concentrations of PGE2 - produce natriuresis (Strandhoy et al, 1974)

Accumulation of ANP• An accumulation of vasoactive substances in BUO that could

contribute to significant post obstructive natriuresis.*

• ANP – increases afferent arteriolar dilation– efferent arteriolar vasoconstriction, thus increasing PGC– decreases the sensitivity of tubuloglomerular feedback– inhibits release of renin, – increases Kf– secreted ANP contributes to a profound diuresis and

natriuresis.

Treatment of

Post Obstructive Diuresis

• Usually – Sodium, urea, and free water are eliminated

and the diuresis subsides after solute and fluid homeostasis is achieved.

–With the return of homeostasis, the period of diuresis ends.

• However, a “pathologic” postobstructive diuresis may ensue, – characterized by inappropriate renal handling

of water or solutes, or both.

• Those who are susceptible to this phenomenon– typically have signs of fluid overload including

edema, congestive heart failure, or hypertension.

– The most common clinical setting is release of urinary retention.

• The intensity of monitoring – depends on presence of risk factors for

postobstructive diuresis and the subject's mental status, renal function, and electrolyte status.

• In the first 24 hours, urine output should be checked hourly.If it's over 200 mL/hour, then 80% of the hourly

output should be replaced intravenously with 0.45% saline.

• After 24 hours of persistent diuresis, total fluids infused should be about 1 L less (or <75%)

than the previous day's output, provided the patient is hemodynamically stable.

• Once the urine output </- 3 L per day, oral fluids should suffice.

Fluid Management

• If there are signs of hypovolemia, then total fluids replaced should be about 0.5 L less, instead of 1 L, than the last 24 hours' output.

• Replacement of electrolytes, e.g. potassium and

magnesium, may be necessary and should be guided by the levels. MP

Obstruction relieved

Risk factors for POD

edema, congestive

heart failure, hypertension

azotemia

Absent, mentally alert, oral fluids

No POD

Discharge

POD

mentally alert, oral fluids

Rfts, na, k daily till diuresis subsides

Risk factors for POD, hypotension, poor cognition

Creat, Na, K, Mg, Urine osmo every 12 hrs

mentally alert, oral fluids

Hypovolemia, dyselectrolytemia

ICU care Majority self-limiting

poor cognitive function

I V below normal maintenance

Hypo-osmolar urine is indicative of a primary water diuresis as opposed to a solute diuresis

• Ureteral obstruction – induces expression of COX-2 in collecting duct

cells and downregulation of AQP2 receptors is mediated by COX-2.

–COX-2 inhibitors prevented the downregulation of AQP2 and significantly diminished postobstructive diuresis in rats.

• In addition, with ureteral obstruction, – cGMP pathway has been demonstrated in both

in vitro and in vivo models to allow membrane insertion of AQP2.

– Sildenafil Citrate elevated intracellular cGMP and facilitate collecting duct accumulation of AQP2.

• Pharmacological manipulation –beneficial or harmful - unclear

Thank you